This invention relates to 3-amido-6-substituted thio-1-azabicyclo[3.2.0]hept-6-en-2-one-7-carboxylic acids (I) and the pharmaceutically acceptable salt and ester derivatives thereof which are useful as antibiotics: ##STR2## wherein: R is R.sup.1 NH; wherein R.sup.1 is hydrogen or an acyl radical known to be effective in the related bicyclic .beta.-lactam antibiotic art, such as, the penicillins, cephalosporins, and 6-amido penems and carbapenems. R.sup.8 is, inter alia, unsubstituted and substituted alkyl, alkenyl, aryl, and aralkyl. The 6-substituent R.sup.8 is defined in greater detail below. Also, for the purpose of defining R.sup.8, European Pat. Appln. No. 80102076.9 (filed Apr. 18, 1980) is incorporated herein by reference. The cited document discloses certain 1-carbadethiapenem antibiotics bearing a 2-SR.sup.8 side chain; it is the very definition of that side chain (--SR.sup.8, or --R.sup.8) which is incorporated herein by reference. To the extent that the following U.S. patents define R.sup.1 as acyl, they are hereby incorporated herein by reference: U.S. Pat. No. 4,217,453 (issued Aug. 12, 1980); U.S. Pat. No. 4,226,866 (issued Oct. 7, 1980).
This invention also relates to the carboxyl derivatives of I which are antibiotics and which may be represented by the following generic structure (I): ##STR3## wherein X' is oxygen, sulphur or NR' (R'=H or lower alkyl having 1-6 carbon atoms); and R.sup.3' is, hydrogen, or, inter alia is representatively selected to provide the pharmaceutically acceptable salt, ester, anhydride (R.sup.3' is acyl), and amide moieties known in bicyclic .beta.-lactam antibiotic art; R.sup.3' may also be a readily removable blocking group. The definition of R.sup.3' is given in greater detail below.
This invention also relates to processes for the preparation of such compounds I; pharmaceutical compositions comprising such compounds; and to methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.
There is a continuing need for new antibiotics. For unfortunately, there is no static effectiveness of any given antibiotic because continued wide scale usage selectively gives rise to resistant strains of pathogens. In addition, the known antibiotics suffer from the disadvantage of being effective only against certain types of microorganisms. Accordingly, the search for new antibiotics continues.
Thus, it is an object of the present invention to provide a novel class of antibiotics which are useful in animal and human therapy and in inaminate systems. These antibiotics are active against a broad range of pathogens which representatively include both Gram positive bacteria such as S. aureus, Strep. pyogenes, and B. subtilis, and Gram negative bacteria such as E. coli, Pseudomonas, Proteus morganii, Serratia, and Klebsiella. Further objects of this invention are to provide chemical processes for the preparation of such antibiotics and their nontoxic, pharmaceutically acceptable salts; pharmaceutical compositions comprising such antibiotics; and to provide methods of treatment comprising administering such antibiotics and compositions when an antibiotic effect is indicated.